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Type I Angiotensin II Receptor Blockade Reduces Uremia‐Induced Deterioration of Bone Material Properties
Author(s) -
Wakamatsu Takuya,
Iwasaki Yoshiko,
Yamamoto Suguru,
Matsuo Koji,
Goto Shin,
Narita Ichiei,
Kazama Junichiro J,
Tanaka Kennichi,
Ito Akemi,
Ozasa Ryosuke,
Nakano Takayoshi,
Miyakoshi Chisato,
Onishi Yoshihiro,
Fukuma Shingo,
Fukuhara Shunichi,
Yamato Hideyuki,
Fukagawa Masafumi,
Akizawa Tadao
Publication year - 2021
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.4159
Subject(s) - pentosidine , osteocyte , olmesartan , oxidative stress , medicine , endocrinology , angiotensin ii , bone mineral , blockade , amlodipine , osteoblast , receptor , chemistry , glycation , osteoporosis , in vitro , biochemistry , blood pressure
ABSTRACT Chronic kidney disease (CKD) is associated with a high incidence of fractures. However, the pathophysiology of this disease is not fully understood, and limited therapeutic interventions are available. This study aimed to determine the impact of type 1 angiotensin II receptor blockade (AT‐1RB) on preventing CKD‐related fragility fractures and elucidate its pharmacological mechanisms. AT‐1RB use was associated with a lower risk of hospitalization due to fractures in 3276 patients undergoing maintenance hemodialysis. In nephrectomized rats, administration of olmesartan suppressed osteocyte apoptosis, skeletal pentosidine accumulation, and apatite disorientation, and partially inhibited the progression of the bone elastic mechanical properties, while the bone mass was unchanged. Olmesartan suppressed angiotensin II‐dependent oxidation stress and apoptosis in primary cultured osteocytes in vitro. In conclusion, angiotensin II‐dependent intraskeletal oxidation stress deteriorated the bone elastic mechanical properties by promoting osteocyte apoptosis and pentosidine accumulation. Thus, AT‐1RB contributes to the underlying pathogenesis of abnormal bone quality in the setting of CKD, possibly by oxidative stress. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).